Myosin light chain and caldesmon phosphorylation in arterial muscle stimulated with endothelin-1.
Endothelin-1 contracts porcine carotid arterial smooth muscle with an ED50 of 10 nM. Contraction is associated with phosphorylation of the 20,000 dalton-regulatory light chain subunits of vascular myosin. Phosphopeptide mapping of light chains isolated from 32PO4-loaded muscle strips stimulated by endothelin-1 (5 x 10(-8) M) and comparison with maps generated from light chains phosphorylated in vitro or muscles stimulated with KCl (110 mM) or angiotensin-II (5 x 10(-8) M) indicates that Ca2(+)-calmodulin activation of myosin light chain kinase is a biochemical pathway stimulated by all three agonists. However, a small amount of phosphate (17%) was detected in a light chain peptide phosphorylated by protein kinase C. Endothelin-1 also stimulated phosphorylation of the thin filament protein, caldesmon, (from 0.35 mol PO4/mol caldesmon to 0.52 mol PO4/mol). Collectively, these results provide evidence that the effects of endothelin-1 on force generation and maintenance in vascular muscle may be dependent upon myosin light chain phosphorylation by Ca2+ calmodulin--requiring myosin light chain kinase and upon a thin filament mechanism that is modulated by phosphorylation of caldesmon.
Adam
L P
LP
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202.
Milio
L
L
Brengle
B
B
Hathaway
D R
DR
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D002148:Calmodulin-Binding Proteins; D016232:Endothelins; D000804:Angiotensin II; D011189:Potassium Chloride; D009218:Myosins